Jean-Pierre Cedoz

Serum levels of MMP-3 and cathepsin K in patients with ankylosing spondylitis: Effect of TNFα antagonist therapy ☆

OBJECTIVE To measure serum levels of MMP-3 and cathepsin K in patients with ankylosing spondylitis (AS) and in controls and to look for changes in these variables during TNFalpha antagonist therapy. METHODS We prospectively studied a group of patients who met New York criteria for AS and a group of healthy volunteers. We recorded age, disease duration, main features of the disease, BASDAI, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP). Serum MMP-3 and cathepsin K were assayed in duplicate using ELISA kits (Quantikine MMP-3, R&D Systems; and Cathepsin K, Biomedica). We also assayed IL-17 (Quantikine IL-17, R&D Systems) and BMP-7 (human BMP-7 DuoSet, R&D Systems). In patients treated with TNFalpha antagonists, the assays were repeated 10 weeks after treatment initiation. The Mann-Whitney test was used for between-group comparisons and the Wilcoxon test for evaluations of changes under treatment. Correlation testing was performed. P-values less than 0.05 were considered significant. RESULTS We studied 23 outpatients with AS and 21 controls, with mean age of 39.9 years and 41.2 years, respectively (NS). Disease duration was 10.1 years (1.3); most patients had axial disease (n=21) and carried HLA-B27 (n=19). At baseline, the mean BASDAI was 44.1 mm (4.1) and the mean CRP level was 22.3 mg/L (4.7). Serum MMP-3 levels were significantly higher in the patients than in the controls (4.71 vs. 2.79 ng/ml, P=0.04); levels were also higher for cathepsin K (6.4 vs. 3.6 pg/ml) and IL-17 (60.4 vs. 32 pg/ml), but the differences were not statistically significant. No difference was noted for BMP-7. The only positive correlation was between the ESR and the CRP level (P=0.0002). Thirteen patients were evaluated 10 weeks into TNFalpha antagonist therapy (adalimumab, n=7; etanercept, n=4; or infliximab, n=2). Serum MMP-3 decreased significantly (P=0.04); significant decreases were also noted for the ESR, CRP, and BASDAI. CONCLUSION MMP-3 is significantly increased in patients with active AS but fails to correlate significantly with conventional variables used to assess disease activity. TNFalpha antagonist therapy induces a significant decrease in MMP-3 levels, together with decreases in conventional variables (ESR, CRP, and BASDAI). MMP-3 may be a biomarker for disease activity in AS but supplies no additional information to the clinician.

Resveratrol, a sirtuin 1 activator, increases IL-6 production by peripheral blood mononuclear cells of patients with knee osteoarthritis

BackgroundSirtuin 1 (Sirt1) is a nuclear enzyme from the class III histone deacetylases that modulates gene expression and is involved in bone and cartilage remodeling. The goal of our study was to evaluate Sirt1 activity in peripheral blood mononuclear cells in patients with osteoarthritis in comparison with control patients, and to determine the relationship between Sirt1 activity and production of TNFα, IL-6 and IL-8 by peripheral blood mononuclear cells after ex vivo treatment with resveratrol, a Sirt1 activator.ResultsA prospective study was performed to compare the activity of Sirt1 in patients with primary osteoarthritis of the knee (American College of Rheumatology criteria) with its activity in controls. Peripheral blood mononuclear cells were isolated from peripheral blood, and Sirt1 activity evaluated from cytoplasmic and nuclear compartments using a fluorometric assay. Culture supernatant levels of TNFα, IL-6, and IL-8 were quantified before and after resveratrol ex vivo treatment. Nineteen patients with symptomatic knee osteoarthritis (age 64 ±9 years) and 18 controls (age 54 ±13 years) were included. No differences were found in cytoplasmic or nuclear Sirt1 activity between patients and controls. After resveratrol treatment, no changes in TNFα or IL-8 levels were found, but a significant dose-dependent increase in IL-6 levels was demonstrated in patients with osteoarthritis, but not controls. Sirt1 activity did not correlate with clinical activity (Lequesne’s index) or inflammation (erythrocyte sedimentation rate, C-reactive protein).ConclusionSirt1 activity (cytoplasmic and nuclear) from peripheral blood mononuclear cells did not differ between patients with osteoarthritis and controls. Ex vivo treatment of peripheral blood mononuclear cells with resveratrol was associated with a dose-dependent increase in IL-6 levels only in patients with osteoarthritis.

Thrombin generation in rheumatoid arthritis

Joint Bone Spine - In Press.Proof corrected by the author Available online since samedi 2 juin 2012